A genetic risk score predicts coronary artery disease in familial hypercholesterolaemia: enhancing the precision of risk assessment

Research output: Contribution to journalArticle

Abstract

Familial hypercholesterolaemia (FH) is associated with increased risk of coronary artery disease (CAD), however, risk prediction and stratification remains a challenge. Genetic risk scores (GRS) may have utility in identifying FH patients at high CAD risk.
The study included 811 patients attending the lipid disorders clinic at Royal Perth Hospital with mutation‐positive (n=251) and mutation‐negative (n=560) FH. Patients were genotyped for a GRS previously associated with CAD. Associations between the GRS, clinical characteristics and CAD were assessed using regression analyses.
The average age of patients was 49.6 years and 44.1% were male. The GRS was associated with increased odds of a CAD event in mutation‐positive (OR=3.3; 95% CI=1.3‐8.2; p=0.009) and mutation‐negative FH patients (OR=1.8; 95% CI= 1.0‐3.3; p=0.039) after adjusting for established predictors of CAD risk. The GRS was associated with greater subclinical atherosclerosis as assessed by coronary artery calcium score (p=0.039).
A high GRS was associated with CAD defined clinically and angiographically in FH patients. High GRS patients may benefit from more intensive management including lifestyle modification and aggressive lipid‐lowering therapy. Further assessment of the utility of the GRS requires investigation in prospective cohorts, including its role in influencing the management of FH patients in the clinic.
Original languageEnglish
JournalClinical Genetics
DOIs
Publication statusE-pub ahead of print - 30 Sep 2019

Fingerprint

Hyperlipoproteinemia Type II
Coronary Artery Disease
Life Style
Atherosclerosis
Coronary Vessels
Regression Analysis

Cite this

@article{fc99121ded45418abcf893022f9c8291,
title = "A genetic risk score predicts coronary artery disease in familial hypercholesterolaemia: enhancing the precision of risk assessment",
abstract = "Familial hypercholesterolaemia (FH) is associated with increased risk of coronary artery disease (CAD), however, risk prediction and stratification remains a challenge. Genetic risk scores (GRS) may have utility in identifying FH patients at high CAD risk.The study included 811 patients attending the lipid disorders clinic at Royal Perth Hospital with mutation‐positive (n=251) and mutation‐negative (n=560) FH. Patients were genotyped for a GRS previously associated with CAD. Associations between the GRS, clinical characteristics and CAD were assessed using regression analyses.The average age of patients was 49.6 years and 44.1{\%} were male. The GRS was associated with increased odds of a CAD event in mutation‐positive (OR=3.3; 95{\%} CI=1.3‐8.2; p=0.009) and mutation‐negative FH patients (OR=1.8; 95{\%} CI= 1.0‐3.3; p=0.039) after adjusting for established predictors of CAD risk. The GRS was associated with greater subclinical atherosclerosis as assessed by coronary artery calcium score (p=0.039).A high GRS was associated with CAD defined clinically and angiographically in FH patients. High GRS patients may benefit from more intensive management including lifestyle modification and aggressive lipid‐lowering therapy. Further assessment of the utility of the GRS requires investigation in prospective cohorts, including its role in influencing the management of FH patients in the clinic.",
author = "Ellis, {Katrina L.} and Hooper, {Amanda J.} and Jing Pang and Chan, {Dick C.} and Burnett, {John R.} and Bell, {Damon A.} and Schultz, {Carl J.} and Moses, {Eric K.} and Watts, {Gerald F.}",
year = "2019",
month = "9",
day = "30",
doi = "10.1111/cge.13648",
language = "English",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "MUNKSGAARD INT PUBL LTD",

}

TY - JOUR

T1 - A genetic risk score predicts coronary artery disease in familial hypercholesterolaemia

T2 - enhancing the precision of risk assessment

AU - Ellis, Katrina L.

AU - Hooper, Amanda J.

AU - Pang, Jing

AU - Chan, Dick C.

AU - Burnett, John R.

AU - Bell, Damon A.

AU - Schultz, Carl J.

AU - Moses, Eric K.

AU - Watts, Gerald F.

PY - 2019/9/30

Y1 - 2019/9/30

N2 - Familial hypercholesterolaemia (FH) is associated with increased risk of coronary artery disease (CAD), however, risk prediction and stratification remains a challenge. Genetic risk scores (GRS) may have utility in identifying FH patients at high CAD risk.The study included 811 patients attending the lipid disorders clinic at Royal Perth Hospital with mutation‐positive (n=251) and mutation‐negative (n=560) FH. Patients were genotyped for a GRS previously associated with CAD. Associations between the GRS, clinical characteristics and CAD were assessed using regression analyses.The average age of patients was 49.6 years and 44.1% were male. The GRS was associated with increased odds of a CAD event in mutation‐positive (OR=3.3; 95% CI=1.3‐8.2; p=0.009) and mutation‐negative FH patients (OR=1.8; 95% CI= 1.0‐3.3; p=0.039) after adjusting for established predictors of CAD risk. The GRS was associated with greater subclinical atherosclerosis as assessed by coronary artery calcium score (p=0.039).A high GRS was associated with CAD defined clinically and angiographically in FH patients. High GRS patients may benefit from more intensive management including lifestyle modification and aggressive lipid‐lowering therapy. Further assessment of the utility of the GRS requires investigation in prospective cohorts, including its role in influencing the management of FH patients in the clinic.

AB - Familial hypercholesterolaemia (FH) is associated with increased risk of coronary artery disease (CAD), however, risk prediction and stratification remains a challenge. Genetic risk scores (GRS) may have utility in identifying FH patients at high CAD risk.The study included 811 patients attending the lipid disorders clinic at Royal Perth Hospital with mutation‐positive (n=251) and mutation‐negative (n=560) FH. Patients were genotyped for a GRS previously associated with CAD. Associations between the GRS, clinical characteristics and CAD were assessed using regression analyses.The average age of patients was 49.6 years and 44.1% were male. The GRS was associated with increased odds of a CAD event in mutation‐positive (OR=3.3; 95% CI=1.3‐8.2; p=0.009) and mutation‐negative FH patients (OR=1.8; 95% CI= 1.0‐3.3; p=0.039) after adjusting for established predictors of CAD risk. The GRS was associated with greater subclinical atherosclerosis as assessed by coronary artery calcium score (p=0.039).A high GRS was associated with CAD defined clinically and angiographically in FH patients. High GRS patients may benefit from more intensive management including lifestyle modification and aggressive lipid‐lowering therapy. Further assessment of the utility of the GRS requires investigation in prospective cohorts, including its role in influencing the management of FH patients in the clinic.

U2 - 10.1111/cge.13648

DO - 10.1111/cge.13648

M3 - Article

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

ER -